Quantitative morphometric techniques will be used to study structural alterations of the myocardium during the development of cardiac hypertrophy in the rat secondary to various stimuli. The spontaneous hypertensive rat (SHR) will be studied as a model of genetically controlled hypertension and cardiac hypertrophy. Hypertension is prevented in SHR by treatment with nerve growth factor antiserum or 6-hydroxydopamine, but hypertrophy is not prevented. This fact allows the separation of hypertensive effects on the hypertrophic myocardium. Isolated heart muscle cells will be prepared by collagenase perfusion of the heart, and the size and shape of the isolated cells quantitatively evaluated from light microscopic preparations. Electron microscopic quantitative stereology will be conducted on perfusion fixed tissue to detect abnormalities in cell organelles including mitochondria, myofibrils, intercalated discs and Z-bands. Morphologic alterations in SHR will be compared with similar data obtained for normally growing normotensive Wistar Kyoto control rats, another experimental hypertension model (renal artery stenosis), and a model of cardiac hypertrophy induced by exposure to carbon monoxide. The use of these different models of cardiac hypertrophy will allow identification of morphologic alterations with various functional states and may provide clues to mechanisms involved in the development of "pathologic" cardiac hypertrophy.